RESUMO
Successful COVID-19 prevention requires additional measures beyond vaccination, social distancing, and masking. A nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (COVITRAP) was developed to strengthen other COVID-19 preventive arsenals. Here, we evaluated its pseudovirus neutralization potencies, preclinical and clinical safety profiles, and intranasal SARS-CoV-2 inhibitory effects in healthy volunteers (NCT05358873). COVITRAP exhibited broadly potent neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 g/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, Ancestral, Delta, Omicron BA.1, Omicron BA.2, Omicron BA.4/5, and Omicron BA.2.75. It demonstrated satisfactory preclinical safety profiles based on evaluations of in vitro cytotoxicity, skin sensitization, intracutaneous reactivity, and systemic toxicity. Its intranasal administration in rats did not yield any detected circulatory levels of the human IgG1 anti-SARS-CoV-2 antibodies at any time point during the 120 hours of follow-up. A double-blind, randomized, placebo-controlled trial (RCT) was conducted on 36 healthy volunteers who received either COVITRAP or a normal saline nasal spray at a 3:1 ratio. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. COVITRAP was well tolerated, with no significant adverse effects in healthy volunteers for the entire 14 days of the study. The intranasal SARS-CoV-2 inhibitory effects of COVITRAP were evaluated in nasal fluids taken from volunteers pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SARS-CoV-2 inhibitory effects in nasal fluids collected immediately or six hours after COVITRAP application were significantly increased from baseline for all three variants tested, including Ancestral, Delta, and Omicron BA.2. In conclusion, COVITRAP was safe for intranasal use in humans to provide SARS-CoV-2 inhibitory effects in nasal fluids that lasted at least six hours. Therefore, COVITRAP can be considered an integral instrument for COVID-19 prevention.
RESUMO
ImportanceInactivated vaccine (CoronaVac) and chimpanzee adenovirus-vector vaccine (ChAdOx1) have been more available in resource-limited settings. However, the data comparing between these two vaccines in the same setting are limited. ObjectivesTo determine adverse events (AEs) and immunogenicity of CoronaVac and ChAdOx1 in health care workers (HCWs). DesignThis prospective study was conducted from February to July 2021. SettingA single center, university-based tertiary care center in Bangkok. ParticipantsHealthy HCWs. ExposureTwo doses of CoronaVac (4 weeks apart) or ChAdOx1 (8 weeks apart) intramuscularly. Main Outcomes and MeasuresSelf-reported AEs were collected for 7 days following each vaccination using electronic diary. The immunogenicity was determined by the level of IgG antibodies against receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S1 subunit). The 50% plaque reduction neutralization tests against original Wuhan strain and circulating VOCs were performed in subset of samples at 2 weeks after the second dose. ResultsOf the 360 HCWs, 180 received each vaccine. The median (interquartile range: IQR) age was 35 (29-44) years old and 84.2% were female. Participants who received ChAdOx1 reported higher frequency of AEs than those received CoronaVac after both the first dose (84.4% vs. 66.1%, P < 0.001) and second dose (75.6% vs. 60.6%, P = 0.002), with more AEs in those younger than 30 years of age for both vaccines. The seroconversion rate was 75.6% and 100% following the first dose of CoronaVac and ChAdOx1, respectively. All participants seroconverted at 2 weeks after the second dose. The anti-SARS-CoV-2 RBD IgG levels induced by CoronaVac was lower than ChAdOX1 with geometric means of 164.4 and 278.5 BAU/mL, respectively (P = 0.0066). Both vaccines induced similar levels of neutralizing antibodies against the Wuhan strain, geometric mean titer (GMT) of 337.4 vs 331.2; however, CoronaVac induced significantly lower GMT against Alpha (23.1 vs. 92.5), Delta (21.2 vs. 69.7), and Beta (10.2 vs. 43.6) variants, respectively. Conclusions and RelevanceCoronaVac induces lower measurable antibodies but with lower frequency of AEs than ChAdOx1. The low neutralizing antibodies against the circulating VOCs induced by CoronaVac supports the need for earlier boosting to prevent breakthrough infections. Trial RegistrationTCTR20210720002 https://www.thaiclinicaltrials.org/ QuestionWhat is the difference between CoronaVac and ChAdOx1 vaccines on safety and immunogenicity against the circulating variants of concern (VOCs) in the same setting? FindingsThis prospective study in 360 healthy health care workers reported higher frequency of adverse events following ChAdOx1 than CoronaVac particularly in those younger than 30 years old. The ChAdOx1 induced 3.3-4.3 times higher neutralising antibodies against VOCs than CoronaVac. MeaningThe 2-dose CoronaVac vaccination induced significantly lower level of neutralizing antibody against the circulating VOCs. An earlier booster may be needed to prevent breakthrough infection.
